- Email: [email protected]
Cortical gray matter volume deficits in women with schizophrenia
95
negative and cognitive syndromes is in its infancy. In this study, we examine their relation to brain structure changes. Methods: 40 subjects with schizophrenia (DSM-III-R) and 25 healthy volunteers were recruited. Positive symptoms were rated on the CASH, Thought Disorder on the TLC scale and Negative Symptoms on the SANS (drug-free). MRI was done with a 1 T magnet; 5 mm interleaved slices were obtained in coronal plane (TR 0.80, TE 20 ms). Ventricle and brain area were measured semiautomatically. ROIs were outlined by threshold function and the perimeter traced by edge detection. Right, Left and Total VBRs were obtained. ANOVA was used to test group differences and multivariate regression to test the relation between syndromes and ventricle size.
of normally occurring HASC asymmetries seem common in schizophrenia. HASC abnormalities can logically be associated with schizophrenia-related impairments in particular aspects of attention, memory, and motivation which are normally dependent on intact function of dynamic cortical networks.
COEXISTENCE
OF IDIOPATHIC
PARKINSON'S DISEASE AND SCHIZOPHRENIA: A CASE STUDIED WITH PET-FDG C.E. Peyser*, T. N o r d a h l , A. D e s h m u k h
Age Sex VBR Left VBR Right VBR
Subjects (n=25)
Controls (n= 15)
F
31.1 +6.9 yrs m=19, f=6 5.84+2.l 5.93+2.4 4.74+ 1.3
29.06+8.9 yrs m=10, f = 4 4.65+1.2 4.26 4.53+ 1.3 4.36 5.74+2.1 3.12
P
Psychiatry Service, VA Medical Center, 3801 Miranda Avenue, Palo Alto, CA 94304, USA n.s. n.s. <0.04 <0.04 <0.08
There was no significant relation between left, right or total VBR and positive, negative or cognitive syndromes. Discussion: The findings suggest diffuse and left hemispheric pathology in schizophrenia. While our previous studies of attention have supported the cognitive syndrome concept, the current results suggest that enlarged ventricles are not specifically associated with any syndrome. Results on all subjects and brain volumetry will be presented.
HETEROMODAL ASSOCIATION IN SCHIZOPHRENIA
CORTEX
G o d f r e y D. Pearlson*, Patrick E. Barta, T h o m a s E. Schlaepfer, R i c h a r d G. Petty, Allen Y. Tien, lain K. McGilchrist
Psychiatry, Johns Hopkins University, 600 N. Wolfe Street, Meyer 3-166, Baltimore, MD 21287, USA Data from several of this group's recent MRI morphometric studies will be presented in support of the hypothesis that schizophrenia represents the clinical manifestations of disorders in which disruption of the heteromodal association cortical loop (HASC) is the final common pathway. The HASC is an integrated system of highly reciprocally interconnected regions of higher-order polymodal association neocortex, which is normally of critical importance in coordinating many sensory, motor, and behavioral activities. Its major components include the dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), and the inferior parietal lobule (IPL). Results from a series of related recent in-vivo morphometric MRI studies will be used to document disproportionate disturbances in size and symmetry of HASC regions in schizophrenia, which exceed both generalized brain size reductions, and reduced overall volume of cortical gray matter. Disturbances
There are few reports of patients with both schizophrenia and idiopathic Parkinson's disease (PD) despite challenging diagnostic and treatment issues. We evaluated XY, a man who in his twenties developed auditory hallucinations and paranoid delusions accompanied by a marked decline in social function. XY remained disabled despite neuroleptic treatment. Right sided hemi-Parkinson's emerged at age 62 while taking prolixin decanoate. Tremor and rigidity worsened despite cessation of neuroleptic treatment for over two years; PD was diagnosed. Bilateral rigidity and tremor without bradykinesia developed, with markedly right-sided predominance. When examined at age 66, his only psychotropic medication was diazepam, 4 mg daily. He had never been treated with L-dopa and during the studies described he took no antiParkinsonian medication. Although guarded in reported psychiatric symptoms, XY described troublesome auditory hallucinations; emotional tone was blunted. BPRS score was 37. Brain images were acquired using the PET-FDG technique; MRI was used to select slices and regions of interest for analysis. Cerebral glucose metabolic rate was increased in left striatum, consistent with previous studies of PD patients with predominantly one-sided motor abnormalities. This is the first report of functional imaging in a patient with concurrent schizophrenia and PD. Supported by MH 30854, AA 05965, Department of Veterans Affairs.
CORTICAL GRAY MATTER VOLUME DEFICITS IN WOMEN WITH SCHIZOPHRENIA J. Lauriello, A. Hoff, M. Weineke, S. D e M e n t , W.O. F a u s t m a n , E.V. Sullivan, K.O. Lim, A. Pfefferbaum*
Department of Psychiatry, D VA and Stanford University School of Medicine, Palo Alto, CA 94304, USA Widespread cortical tissue volume deficit, selective to gray matter, has been observed in schizophrenic men, but whether
96
schizophrenic women show this brain dysmorphology is not established. Gender differences do occur in the clinical course and prognosis of schizophrenia. Furthermore, since gender differences are present in normal brain morphology, results from studies solely of male patients do not necessarily generalize to female patients. In this study, we collected quantitative MRI data in 14 women with DSM-III-R schizophrenia, recruited from a state hospital (age=37.6+8.1 years; education= 11.6+2.3 years). MRI volumes of the patients were adjusted for normal variation in head size and age, established from 28 healthy women, and were expressed as Z-scores. Compared with age-matched women controls, the schizophrenic women had a greater than one standard deviation cortical volume deficit selective to gray matter (p <0.01) and normal white matter volume. In addition, volumes of the cortical sulci ( p < 0.05 ) and lateral ( p < 0.012) and third ventricles ( p < 0.05) were significantly enlarged. The pattern of brain dysmorphology with respect to overall tissue, sulcal, and ventricular volumes observed in this sample of schizophrenic women was similar to that observed previously in various groups of schizophrenic men. Supported by MH 30854, AA 05965, State of California Department of Mental Health, Department of Veterans Affairs.
D 2 OCCUPANCY AND DOPAMINE RELEASE DETERMINED BY 123I-IBZM SPECT FOLLOWING
CLOZAPINE
DOSE REDUCTION
99m Tc-HMPAO IN PATIENTS
SPET NEUROIMAGING WITH
SCHIZOPHRENIA
WHO HAVE ABNORMAL SACCADIC EYE-MOVEMENT DISTRACTIBILITY B.K. Puri*, T.J. Crawford, K.S. Nijran, B. Jones, C. K e n n a r d , S.W. Lewis
Department of Psychiatry, Charing Cross & Westminster Medical School, St. Dunstan's Road, London I4168RF, UK Recent research has shown that some patients with schizophrenia have a severe impairment in the suppression of reflexive saccadic eye movements in the anti-saccade task. This saccadic distractibility has previously been found in patients with lesions of dorsolateral prefrontal cortex, implicating an abnormality of prefrontal cortex. The objective of the present study was to determine the contribution of these and other areas to the antisaccadic abnormality in schizophrenia by functional neuroimaging. Using 99m-technetium-HMPAO high resolution multidetector single-photon emission tomography, regional cerebral blood flow (rCBF) during performance of the antisaccade eye-movement task was compared, by statistical parametric mapping (SPM), in ten male schizophrenic patients on stable antipsychotic medication who had a high distractibility error rate on the task, and eight similar patients who had normal distractibility error rates. Compared to the normal error group, the patients with high error rates showed significantly decreased rCBF bilaterally, in the anterior cingulate, insula, and in left striatum. These same patients also had increased perseverative errors in the Wisconsin Card Sort Test. An analysis was also carried out, using SPM, or rCBF in the psychomotor poverty, disorganization, and reality distortion syndromes.
D. Pickar, T.-P. Su, R. Coppola, C.S. Lee, J.K. Hsiao, A. Breier, D.R. Weinberger
Experimental Therapeutics Branch, NIMH, NIH, Bethesda, MD 20892-1380, USA Estimated striatal D 2 occupancy was determined using 1231IBZM SPECT in 13 DSM-III diagnosed patients with schizophrenia who were successfully maintained on clozapine treatment as outpatients. Estimated D z occupancy (determined by the method of Farde) ranged broadly from 25o/o- > 80% with a curvilinear relation between clozapine blood level and estimated occupancy. There was no significant relationship between estimated D 2 occupancy and symptomatology. Relatively low striatal D 2 occupancy may be sufficient to maintain good therapeutic response to clozapine in some patients. Following clozapine dose reduction of >50% (510+184mg/day to 189+79mg/day for 12.4+8.3 days), positive and negative symptoms significantly worsened and estimated Dz occupancy significantly decreased. At reduced clozapine doses, psychotic symptoms were positively correlated with IBZM displacement (after removing the effects of clozapine blood level), suggesting the possibility of IBZM displacement by dopamine release associated with symptom exacerbation due to clozapine dose reduction.
PINEAL GLAND VOLUME IN SCHIZOPHRENIA: AN MRI STUDY R a j a p r a b h a k a r a n R a j a r e t h i n a m * , Sanjay G u p t a , N a n c y C. A n d r e a s e n
Mental Health Clinical Research Center, JPP, University of Iowa, College of Medicine, Iowa City, 1,4 52246-1057, USA Abnormal pineal metabolism has been proposed as a possible biological defect in schizophrenia. Studies linking pineal gland and schizophrenia are few and inconclusive. CT studies have reported an association of the pineal calcification to early onset of the illness and Tardive Dyskinesia. No previous study has focused on pineal gland volume. This study was designed to investigate volumetric differences using MRI. Patients with a DSM-III-R diagnosis of schizophrenia or schizophreniform disorder (n =45) and normal controls (n=86) were scanned using a 1.5 Tesla scanner. This yielded 1.5 mm thick T1 weighted slices with no gap. The volume was obtained by blind manual tracing of the gland using locally developed software, BRAINS. The inter-rater reliability (n= 25) yielded an intraclass r of 0.92.
negative and cognitive syndromes is in its infancy. In this study, we examine their relation to brain structure changes. Methods: 40 subjects with schizophrenia (DSM-III-R) and 25 healthy volunteers were recruited. Positive symptoms were rated on the CASH, Thought Disorder on the TLC scale and Negative Symptoms on the SANS (drug-free). MRI was done with a 1 T magnet; 5 mm interleaved slices were obtained in coronal plane (TR 0.80, TE 20 ms). Ventricle and brain area were measured semiautomatically. ROIs were outlined by threshold function and the perimeter traced by edge detection. Right, Left and Total VBRs were obtained. ANOVA was used to test group differences and multivariate regression to test the relation between syndromes and ventricle size.
of normally occurring HASC asymmetries seem common in schizophrenia. HASC abnormalities can logically be associated with schizophrenia-related impairments in particular aspects of attention, memory, and motivation which are normally dependent on intact function of dynamic cortical networks.
COEXISTENCE
OF IDIOPATHIC
PARKINSON'S DISEASE AND SCHIZOPHRENIA: A CASE STUDIED WITH PET-FDG C.E. Peyser*, T. N o r d a h l , A. D e s h m u k h
Age Sex VBR Left VBR Right VBR
Subjects (n=25)
Controls (n= 15)
F
31.1 +6.9 yrs m=19, f=6 5.84+2.l 5.93+2.4 4.74+ 1.3
29.06+8.9 yrs m=10, f = 4 4.65+1.2 4.26 4.53+ 1.3 4.36 5.74+2.1 3.12
P
Psychiatry Service, VA Medical Center, 3801 Miranda Avenue, Palo Alto, CA 94304, USA n.s. n.s. <0.04 <0.04 <0.08
There was no significant relation between left, right or total VBR and positive, negative or cognitive syndromes. Discussion: The findings suggest diffuse and left hemispheric pathology in schizophrenia. While our previous studies of attention have supported the cognitive syndrome concept, the current results suggest that enlarged ventricles are not specifically associated with any syndrome. Results on all subjects and brain volumetry will be presented.
HETEROMODAL ASSOCIATION IN SCHIZOPHRENIA
CORTEX
G o d f r e y D. Pearlson*, Patrick E. Barta, T h o m a s E. Schlaepfer, R i c h a r d G. Petty, Allen Y. Tien, lain K. McGilchrist
Psychiatry, Johns Hopkins University, 600 N. Wolfe Street, Meyer 3-166, Baltimore, MD 21287, USA Data from several of this group's recent MRI morphometric studies will be presented in support of the hypothesis that schizophrenia represents the clinical manifestations of disorders in which disruption of the heteromodal association cortical loop (HASC) is the final common pathway. The HASC is an integrated system of highly reciprocally interconnected regions of higher-order polymodal association neocortex, which is normally of critical importance in coordinating many sensory, motor, and behavioral activities. Its major components include the dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), and the inferior parietal lobule (IPL). Results from a series of related recent in-vivo morphometric MRI studies will be used to document disproportionate disturbances in size and symmetry of HASC regions in schizophrenia, which exceed both generalized brain size reductions, and reduced overall volume of cortical gray matter. Disturbances
There are few reports of patients with both schizophrenia and idiopathic Parkinson's disease (PD) despite challenging diagnostic and treatment issues. We evaluated XY, a man who in his twenties developed auditory hallucinations and paranoid delusions accompanied by a marked decline in social function. XY remained disabled despite neuroleptic treatment. Right sided hemi-Parkinson's emerged at age 62 while taking prolixin decanoate. Tremor and rigidity worsened despite cessation of neuroleptic treatment for over two years; PD was diagnosed. Bilateral rigidity and tremor without bradykinesia developed, with markedly right-sided predominance. When examined at age 66, his only psychotropic medication was diazepam, 4 mg daily. He had never been treated with L-dopa and during the studies described he took no antiParkinsonian medication. Although guarded in reported psychiatric symptoms, XY described troublesome auditory hallucinations; emotional tone was blunted. BPRS score was 37. Brain images were acquired using the PET-FDG technique; MRI was used to select slices and regions of interest for analysis. Cerebral glucose metabolic rate was increased in left striatum, consistent with previous studies of PD patients with predominantly one-sided motor abnormalities. This is the first report of functional imaging in a patient with concurrent schizophrenia and PD. Supported by MH 30854, AA 05965, Department of Veterans Affairs.
CORTICAL GRAY MATTER VOLUME DEFICITS IN WOMEN WITH SCHIZOPHRENIA J. Lauriello, A. Hoff, M. Weineke, S. D e M e n t , W.O. F a u s t m a n , E.V. Sullivan, K.O. Lim, A. Pfefferbaum*
Department of Psychiatry, D VA and Stanford University School of Medicine, Palo Alto, CA 94304, USA Widespread cortical tissue volume deficit, selective to gray matter, has been observed in schizophrenic men, but whether
96
schizophrenic women show this brain dysmorphology is not established. Gender differences do occur in the clinical course and prognosis of schizophrenia. Furthermore, since gender differences are present in normal brain morphology, results from studies solely of male patients do not necessarily generalize to female patients. In this study, we collected quantitative MRI data in 14 women with DSM-III-R schizophrenia, recruited from a state hospital (age=37.6+8.1 years; education= 11.6+2.3 years). MRI volumes of the patients were adjusted for normal variation in head size and age, established from 28 healthy women, and were expressed as Z-scores. Compared with age-matched women controls, the schizophrenic women had a greater than one standard deviation cortical volume deficit selective to gray matter (p <0.01) and normal white matter volume. In addition, volumes of the cortical sulci ( p < 0.05 ) and lateral ( p < 0.012) and third ventricles ( p < 0.05) were significantly enlarged. The pattern of brain dysmorphology with respect to overall tissue, sulcal, and ventricular volumes observed in this sample of schizophrenic women was similar to that observed previously in various groups of schizophrenic men. Supported by MH 30854, AA 05965, State of California Department of Mental Health, Department of Veterans Affairs.
D 2 OCCUPANCY AND DOPAMINE RELEASE DETERMINED BY 123I-IBZM SPECT FOLLOWING
CLOZAPINE
DOSE REDUCTION
99m Tc-HMPAO IN PATIENTS
SPET NEUROIMAGING WITH
SCHIZOPHRENIA
WHO HAVE ABNORMAL SACCADIC EYE-MOVEMENT DISTRACTIBILITY B.K. Puri*, T.J. Crawford, K.S. Nijran, B. Jones, C. K e n n a r d , S.W. Lewis
Department of Psychiatry, Charing Cross & Westminster Medical School, St. Dunstan's Road, London I4168RF, UK Recent research has shown that some patients with schizophrenia have a severe impairment in the suppression of reflexive saccadic eye movements in the anti-saccade task. This saccadic distractibility has previously been found in patients with lesions of dorsolateral prefrontal cortex, implicating an abnormality of prefrontal cortex. The objective of the present study was to determine the contribution of these and other areas to the antisaccadic abnormality in schizophrenia by functional neuroimaging. Using 99m-technetium-HMPAO high resolution multidetector single-photon emission tomography, regional cerebral blood flow (rCBF) during performance of the antisaccade eye-movement task was compared, by statistical parametric mapping (SPM), in ten male schizophrenic patients on stable antipsychotic medication who had a high distractibility error rate on the task, and eight similar patients who had normal distractibility error rates. Compared to the normal error group, the patients with high error rates showed significantly decreased rCBF bilaterally, in the anterior cingulate, insula, and in left striatum. These same patients also had increased perseverative errors in the Wisconsin Card Sort Test. An analysis was also carried out, using SPM, or rCBF in the psychomotor poverty, disorganization, and reality distortion syndromes.
D. Pickar, T.-P. Su, R. Coppola, C.S. Lee, J.K. Hsiao, A. Breier, D.R. Weinberger
Experimental Therapeutics Branch, NIMH, NIH, Bethesda, MD 20892-1380, USA Estimated striatal D 2 occupancy was determined using 1231IBZM SPECT in 13 DSM-III diagnosed patients with schizophrenia who were successfully maintained on clozapine treatment as outpatients. Estimated D z occupancy (determined by the method of Farde) ranged broadly from 25o/o- > 80% with a curvilinear relation between clozapine blood level and estimated occupancy. There was no significant relationship between estimated D 2 occupancy and symptomatology. Relatively low striatal D 2 occupancy may be sufficient to maintain good therapeutic response to clozapine in some patients. Following clozapine dose reduction of >50% (510+184mg/day to 189+79mg/day for 12.4+8.3 days), positive and negative symptoms significantly worsened and estimated Dz occupancy significantly decreased. At reduced clozapine doses, psychotic symptoms were positively correlated with IBZM displacement (after removing the effects of clozapine blood level), suggesting the possibility of IBZM displacement by dopamine release associated with symptom exacerbation due to clozapine dose reduction.
PINEAL GLAND VOLUME IN SCHIZOPHRENIA: AN MRI STUDY R a j a p r a b h a k a r a n R a j a r e t h i n a m * , Sanjay G u p t a , N a n c y C. A n d r e a s e n
Mental Health Clinical Research Center, JPP, University of Iowa, College of Medicine, Iowa City, 1,4 52246-1057, USA Abnormal pineal metabolism has been proposed as a possible biological defect in schizophrenia. Studies linking pineal gland and schizophrenia are few and inconclusive. CT studies have reported an association of the pineal calcification to early onset of the illness and Tardive Dyskinesia. No previous study has focused on pineal gland volume. This study was designed to investigate volumetric differences using MRI. Patients with a DSM-III-R diagnosis of schizophrenia or schizophreniform disorder (n =45) and normal controls (n=86) were scanned using a 1.5 Tesla scanner. This yielded 1.5 mm thick T1 weighted slices with no gap. The volume was obtained by blind manual tracing of the gland using locally developed software, BRAINS. The inter-rater reliability (n= 25) yielded an intraclass r of 0.92.